合成路线:Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II),which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III).The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV).1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII).Finally,intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.
参考文献标题:Piperazinyl-heterocyclic cpds
文献作者:Lowe,J.A.III; Nagel,A.A.(Pfizer Inc.)
参考来源:US 4831031
合成路线:Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II),which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III).The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV).1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII).Finally,intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.
合成路线:The condensation of 1-(1,2-benzoisothiazol-3-yl)piperazine (I) with 6-chloro-5-(2-chloroethyl)-2-indolinone (II) in refluxing water or refluxing methyl isobutyl ketone gives the target indolinone derivative.
参考文献标题:Process for preparing aryl piperazinyl-heterocyclic cpds
文献作者:Bowles,P.(Pfizer Inc.)
参考来源:EP 1029861; JP 1994184143; US 5206366
合成路线:The nitration of 2,5-dichlorotoluene (I) with HNO3 in H2SO4/AcOH gives 2,5-dichloro-4-methylnitrobenzene (II),which is treated with t-butoxybis(dimethylamino)methane (III) in refluxing THF to yield 2,5-dichloro-4-[2-(dimethylamino)vinyl]nitrobenzene (IV).The condensation of (IV) with 1-(1,2-benzoisothiazol-3-yl)piperazine (V) in AcOH affords the disubstituted piperazine (VI),whose double bond is reduced by means of NaBH(OAc)3 in dichloroethane/AcOH to provide the saturated compound (VII).The condensation of (VII) with dimethyl malonate (VIII) by means of KOH in NMP gives the alkylated malonic ester (IX),which is hydrolyzed and monodecarboxylated with refluxing 3N HCl to yield the phenylacetic acid (X).The esterification of (X) with SOCl2 and methanol affords the methyl ester (XI),which is finally cyclized to the target indolone by reduction of its nitro group with sodium hydrosulfite in refluxing THF/ethanol.Alternatively,compound (VII) can be condensed with methyl cyanacetate (XII) by means of KOH in NMP to give the alkylated cyanacetic ester (XIII),which is hydrolyzed with refluxing 3N HCl to afford the already reported phenylacetic acid (X).
参考文献标题:Processes and intermediates for the preparation of 5-[2-(4-(benzoisothiazol-3-yl)-piperazin-1-yl)ethyl]-6-chloro-1,3-dihydro-indol-2-one
文献作者:Urban,F.J.(Pfizer Inc.)
参考来源:WO 9500510
合成路线:Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II),which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III).The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV).1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII).Finally,intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.
参考文献标题:Controlled synthesis of ziprasidone and compsns.thereof
文献作者:Howard,H.R.Jr.; Busch,F.R.; Grobin,A.W.; Leeman,K.R.(Pfizer Products Inc.)
参考来源:WO 0370246
合成路线:The Friedel Crafts condensation of 6-chloroindolin-2-one (I) with 14C labeled 2-chloroacetyl chloride (II) by means of AlCl3 in CS2 gives 6-chloro-5-(2-chloroacetyl)indolin-2-one (III),which is reduced with trimethylsilane in TFA to yield the labeled chloroethyl derivative (IV).Finally,this compound is condensed with 3-(1-piperazinyl)-1,2-benzoisothiazole (V) by means of Na2CO3 in refluxing water to provide the target radiolabeled compound.
合成路线:The bromination of 3-chloro-1,2-benzoisothiazole (I) with Br2 in AcOH using FeCl3 as catalyst gives a mixture of 3,5-dibromo-1,2-benzoisothiazole (II) and 3,7-dibromo-1,2-benzoisothiazole (III) that are separated by flash chromatography.The desired isomer (III) is condensed with piperazine (IV) in refluxing diglyme to yield 7-bromo-3-(1-piperazinyl)-1,2-benzoisothiazole (V),which is condensed with 6-chloro-5-(2-chloroethyl)indolin-2-one (VI) by means of Na2CO3 in refluxing water to afford the brominated adduct (VII).Finally,this compound is debrominated with tritium gas over a Pd/BaSO4 catalyst in THF to provide the target radiolabeled compound.
参考文献标题:Synthesis of H-3- and C-14-labelled CP-88,059: A potent atypical antipsychotic agent
文献作者:Howard,H.R.; Shenk,K.D.; Smolarek,T.A.; Marx,M.H.; Windels,J.H.; Roth,R.W.
参考来源:J Label Compd Radiopharm 1994,34(2),117
合成路线:Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II),which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III).The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV).1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII).Finally,intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.
参考文献标题:Ziprasidone Hydrochloride
文献作者:Seeger,T.F.; Prakash,C.; Howard,H.R.
参考来源:Drugs Fut 1994,19(6),560
产品链接: CAS No. 138982-67-9›› 产品链接: CAS No.146939-27-7››